Suppression of short interfering RNA-mediated gene silencing by the structural proteins of hepatitis C virus.
Viruses have evolved strategies to overcome the antiviral effects of the host at different levels. Besides specific defence mechanisms, the host responds to viral infection via the interferon pathway and also by RNA interference (RNAi). However, several viruses have been identified that suppress RNAi. We addressed the question of whether hepatitis C virus (HCV) suppresses RNAi, using cell lines constitutively expressing green fluorescent protein (GFP) and inducibly expressing HCV proteins. It was found that short interfering RNA-mediated GFP gene silencing was inhibited when the entire HCV polyprotein was expressed. Further studies showed that HCV structural proteins, and in particular envelope protein 2 (E2), were responsible for this inhibition. Co-precipitation assays demonstrated that E2 bound to Argonaute-2 (Ago-2), a member of the RNA-induced silencing complex, RISC. Thus, HCV E2 that interacts with Ago-2 is able to suppress RNAi.
Ji
Jingmin
J
Department of Biomedicine, Institute for Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.
Glaser
Andrea
A
Department of Biomedicine, Institute for Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.
Wernli
Marion
M
Department of Biomedicine, Institute for Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.
Berke
Jan Martin
JM
Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, CH-1011 Lausanne, Switzerland.
Moradpour
Darius
D
Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, CH-1011 Lausanne, Switzerland.
Erb
Peter
P
Department of Biomedicine, Institute for Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.
D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D005819:Genetic Markers; D049452:Green Fluorescent Proteins / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D012516:Osteosarcoma; D034741:RNA, Small Interfering / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
D005819:Genetic Markers; D034741:RNA, Small Interfering; D014764:Viral Proteins; D015678:Viral Structural Proteins; D049452:Green Fluorescent Proteins